Intestinal inflammatory disease is the term used to describe chronic diseases that cause inflammation of the intestines. Diseases such as ulcerative colitis and Crohn's disease are examples of intestinal inflammatory disease. Other diseases which affect the intestines such as irritable bowel disease may be caused by inflammation in part of the intestines.
Ulcerative colitis is an inflammatory disease of the colon. In ulcerative colitis, the lining of the intestinal wall reddens and swells and develops ulcers. The condition is often most severe in the rectal area, which can cause frequent diarrhoea. Additionally mucus and blood may appear in the stool if the lining of the colon is damaged.
Crohn's disease may affect any part of the digestive system, from the mouth to the anus, but it is most common in the lower part of the small bowel or the first part of the large bowel. It often affects more than one part of the bowel leaving normal, unaffected areas in between.
Crohn's disease is a chronic relapsing inflammatory disorder of the gastrointestinal (GI) tract occurring worldwide, most notably in North America and Europe with an incidence of 2-6 per 100,000 per year and a prevalence of 60-80 per 100,000. The onset of disease can occur in any age group but is more common in young adults. Crohn's disease is characterised by mucosal membrane inflammation affecting any part of the GI tract, with the terminal ileum (35%), ileocaecal region (40%) and colon (20%) generally being the most affected areas.
Crohn's disease patients have an increased blood flow in the wall of the bowel; this causes inflammation and ulceration, which extends to the deepest layers of the bowel.
The exact cause of Crohn's disease is not known, but it is thought that the body's immune system overreacts to a virus or bacterium, causing on-going inflammation in the bowel. The disease often tends to run in families.
Crohn's disease is usually a life-long condition, with alternating flare-ups of symptoms and periods of remission. The symptoms include: diarrhoea, up to 10 or 20 times a day; pain, anywhere in the abdomen, and is often described as cramping or colicky. The abdomen may be sore to the touch and swollen; loss of appetite; weight loss; fever; rectal bleeding; anaemia; fissures and abscesses in the anal area.
During a flare-up of symptoms problems in other areas of the body may also occur, such as mouth ulcers, joint pain, eye inflammation, rashes and ulcers on the skin.
With chronic Crohn's disease, severe inflammation may cause complications to develop. This includes a fistula, which is an abnormal connection between the bowel and a neighbouring part of the body, such as the bladder, vagina, or another loop of bowel. Fistulas may lead to recurrent infections of the urinary or genital tracts. Other complications include an abscess (collection of pus) inside the abdomen or a stricture, a narrowing of the bowel caused by scar tissue that can obstruct the passage of material through the bowel. It is also known that patients who have had Crohn's disease for 8 to 10 years are at an increased risk of bowel cancer.
There is no cure for Crohn's disease. Symptoms can be improved with dietary changes, drugs or surgery, or a combination of these.
Medicines to reduce inflammation such as corticosteroids are often used in Crohn's disease along with medicines that suppress the immune system. Anti-diarrhoea medicines, antibiotics and painkillers may also be used during flare-ups.
Existing therapies currently available for use in the treatment of acute active Crohn's disease, particularly corticosteroids, are not universally effective or well tolerated by all patients and/or may not be cost-effective in the long-term. In addition, approximately 45% of patients cannot discontinue corticosteroid treatment without an exacerbation of their disease and consequently, many patients can become tolerant to such drugs although, this is more evident in moderate to severe disease.
Many people with Crohn's disease require surgical treatment at some time to treat complications such as anal abscesses, or fistulae, to remove areas of narrowed, non-functioning bowel, or when drugs are not controlling the disease.
The phytocannabinoid CBD has been ascribed as an anti-inflammatory agent (Fride et al. (2005) and Di Carlo and Izzo (2003).
Massa and Monory (2006) describes the use of the endocannabinoids as natural protectants in inflammatory and gastrointestinal disorders.
Cannabidiol (CBD) was shown to exert an anti-inflammatory effect in the DNBS model of intestinal bowel disease in mice (Borrelli et al. 2009).
Furthermore EP1071417 describes the use of pure cannabidiol. The pure CBD is thought to be useful as an anti-inflammatory agent and much data is provided for its use as a treatment for rheumatoid arthritis.
The applications EP1361864 and EP1542657 suggest that the use of a broad ratio CBD:THC (19:1) product might be useful in the treatment of inflammatory bowel disease.
The application WO 2009/004302 describes a combination of the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD) may be useful in the treatment of an inflammatory bowel disease. The ratio of THC to CBD used is between 1:1 to 1:2.
Intestinal inflammatory disease affects millions of individuals and although major advances have been made in respect to treatment, many patients still receive suboptimal treatment (Colombel et al. 2008).
The application WO 2009/004302 describes a CBD extract for use in the treatment of intestinal inflammatory disorders, the application goes on to disclose that the CBD extract comprises minor amounts of other cannabinoids including CBG, CBC and CBDV.
The patent EP 2,044,935 describes an extract from cannabis that might be useful in the treatment of gastrointestinal inflammatory diseases. The extract may comprise CBG or CBD.
The application WO 02/064109 describes that extracts of THC and CBD may comprise minor amounts of other cannabinoids.
The patent EP 1,559,423 describes the use of acid cannabinoids in inflammatory diseases.
The application GB 2450493 describes the use of CBG in the treatment of many different diseases or conditions dependent on CBG's ability to agonise the CB1 and CB2 receptors.
It is an object of the present invention to provide a new treatment option for intestinal inflammatory diseases, as there is clearly an unmet need for new medications which are able to successfully control these diseases.
It has been observed that the phytocannabinoids tetrahydrocannabivarin (THCV); cannabigerol (CBG); cannabichromene (CBC); and cannabidivarin (CBDV) are effective agents in reducing intestinal inflammation. Such compounds might have utility in the treatment of inflammatory diseases of the intestines such as ulcerative colitis and Crohn's disease.